PMID- 16956324 OWN - NLM STAT- MEDLINE DCOM- 20070129 LR - 20191210 IS - 1470-8728 (Electronic) IS - 0264-6021 (Print) IS - 0264-6021 (Linking) VI - 401 IP - 1 DP - 2007 Jan 1 TI - IOP1, a novel hydrogenase-like protein that modulates hypoxia-inducible factor-1alpha activity. PG - 341-52 AB - A central means by which mammalian cells respond to low oxygen tension is through the activation of the transcription factor HIF-1 (hypoxia-inducible factor-1). Under normoxic conditions, HIF-1alpha (the alpha subunit of HIF-1) is targeted for rapid degradation by the ubiquitin-proteasome pathway. Under hypoxic conditions, this degradation is inhibited, thereby leading to the stabilization and activation of HIF-1alpha. Here, we report the identification of IOP1 (iron-only hydrogenase-like protein 1), a protein homologous with enzymes present in anaerobic organisms that contain a distinctive iron-sulfur cluster. IOP1 is present in a broad range of cell types. Knockdown of IOP1 using siRNA (small interfering RNA) in mammalian cells increases protein levels of HIF-1alpha under both normoxic and hypoxic conditions, and augments hypoxia-induced HRE (hypoxia response element) reporter gene and endogenous HIF-1alpha target gene expressions. We find that IOP1 knockdown up-regulates HIF-1alpha mRNA levels, thereby providing a mechanism by which knockdown induces the observed effects. The results collectively provide evidence that IOP1 is a component of the protein network that regulates HIF-1alpha in mammalian cells. FAU - Huang, Jianhe AU - Huang J AD - Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. FAU - Song, Daisheng AU - Song D FAU - Flores, Adrian AU - Flores A FAU - Zhao, Quan AU - Zhao Q FAU - Mooney, Sharon M AU - Mooney SM FAU - Shaw, Leslie M AU - Shaw LM FAU - Lee, Frank S AU - Lee FS LA - eng GR - R01 CA090261/CA/NCI NIH HHS/United States GR - R01 GM071459/GM/NIGMS NIH HHS/United States GR - R01-CA090261/CA/NCI NIH HHS/United States GR - R01-GM071459/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Biochem J JT - The Biochemical journal JID - 2984726R RN - 0 (CIAO3 protein, human) RN - 0 (Iron-Sulfur Proteins) RN - 0 (Peptide Fragments) RN - 0 (Saccharomyces cerevisiae Proteins) RN - EC 1.12.7.2 (Hydrogenase) SB - IM MH - Amino Acid Sequence MH - Blotting, Northern MH - Conserved Sequence MH - Humans MH - Hydrogenase/chemistry/genetics/*metabolism MH - Iron-Sulfur Proteins MH - Kidney MH - Molecular Sequence Data MH - Peptide Fragments/chemistry/metabolism MH - Saccharomyces cerevisiae/enzymology MH - Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism MH - Sequence Alignment MH - Sequence Homology, Amino Acid PMC - PMC1698691 EDAT- 2006/09/08 09:00 MHDA- 2007/01/30 09:00 PMCR- 2007/07/01 CRDT- 2006/09/08 09:00 PHST- 2006/09/08 09:00 [pubmed] PHST- 2007/01/30 09:00 [medline] PHST- 2006/09/08 09:00 [entrez] PHST- 2007/07/01 00:00 [pmc-release] AID - BJ20060635 [pii] AID - bj4010341 [pii] AID - 10.1042/BJ20060635 [doi] PST - ppublish SO - Biochem J. 2007 Jan 1;401(1):341-52. doi: 10.1042/BJ20060635.